Muscarinic responses of gastric parietal cells

Journal Article · Sat Jun 01 00:00:00 EDT 1991 · Journal of Membrane Biology; (United States)

DOI:https://doi.org/10.1007/BF01872634· OSTI ID:5031394

Wilkes, J M; Kajimura, M; Scott, D R; Hersey, S J; Sachs, G ^[1]

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1. Department of Medicine, University of California, Los Angeles (United States)

Isolated rabbit gastric glands were used to study the nature of the muscarinic cholinergic responses of parietal cells. Carbachol stimulation of acid secretion, as measured by the accumulation of aminopyrine, was inhibited by the M1 antagonist, pirenzepine, with an IC50 of 13 microM; by the M2 antagonist, 11,2-(diethylamino)methyl-1 piperidinyl acetyl-5,11-dihydro-6H-pyrido 2,3-b 1,4 benzodiazepin-6-one (AF-DX 116), with an IC50 of 110 microM; and by the M1/M3 antagonist, diphenyl-acetoxy-4-methylpiperidinemethiodide, with an IC50 of 35 nM. The three antagonists displayed equivalent IC50 values for the inhibition of carbachol-stimulated production of 14CO2 from radiolabeled glucose, which is a measure of the turnover of the H,K-ATPase, the final step of acid secretion. Intracellular calcium levels were measured in gastric glands loaded with FURA 2. Carbachol was shown to both release calcium from an intracellular pool and to promote calcium entry across the plasma membrane. The calcium entry was inhibitable by 20 microM La3+. The relative potency of the three muscarinic antagonists for inhibition of calcium entry was essentially the same as for inhibition of acid secretion or pump related glucose oxidation. Image analysis of the glands showed the effects of carbachol, and of the antagonists, on intracellular calcium were occurring largely in the parietal cell. The rise in cell calcium due to release of calcium from intracellular stores was inhibited by 4-DAMP with an IC50 of 1.7 nM, suggesting that the release pathway was regulated by a low affinity M3 muscarinic receptor or state; Ca entry and acid secretion are regulated by a high affinity M3 muscarinic receptor or state, inhibited by higher 4-DAMP concentrations, suggesting that it is the steady-state elevation of Ca that is related to parietal cell function rather than the (Ca)i transient.

• OSTI ID: 5031394
• Journal Information: Journal of Membrane Biology; (United States), Vol. 122:2; ISSN 0022-2631
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ACETYLCHOLINE
RECEPTORS
CALCIUM
MEMBRANE TRANSPORT
GASTRIC ACID
SECRETION
PARASYMPATHOLYTICS
BIOCHEMICAL REACTION KINETICS
ATP-ASE
BIOLOGICAL PATHWAYS
CARBON 14 COMPOUNDS
GLUCOSE
IMAGE PROCESSING
INHIBITION
PIPERIDINES
RABBITS
STOMACH
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ACID ANHYDRASES
ALDEHYDES
ALKALINE EARTH METALS
AMINES
AMMONIUM COMPOUNDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
BIOLOGICAL MATERIALS
BODY
BODY FLUIDS
CARBOHYDRATES
CARBON COMPOUNDS
DIGESTIVE SYSTEM
DRUGS
ELEMENTS
ENZYMES
ESTERS
GASTROINTESTINAL TRACT
HETEROCYCLIC COMPOUNDS
HEXOSES
HYDROGEN COMPOUNDS
HYDROLASES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
METALS
MONOSACCHARIDES
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PARASYMPATHOMIMETICS
PHOSPHOHYDROLASES
PROCESSING
PROTEINS
PYRIDINES
QUATERNARY COMPOUNDS
REACTION KINETICS
SACCHARIDES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques